SELF-ASSEMBLY OF THE BRAIN MAP-2 MICROTUBULE-BINDING REGION INTO POLYMERIC STRUCTURES RESEMBLING ALZHEIMER FILAMENTS

The neuronal microtubule-associated protein known as MAP-2 has not bee n considered to be a subunit of paired helical filaments (PHFs) in neu rofibrillary tangles seen in Alzheimer's Disease. We now describe the assembly of paired helical filament-like structures from MAP-2's 203-r esidue microtubule-binding region (MTBR). SDS gel electrophoresis and equilibrium ultracentrifugation suggest that a dimeric form, cross-lin ked by an interchain disulfide, is involved in polymerization. MAP-2 M TBR polymers bind thioflavin-S, a dye used to histochemically localize Alzheimer neurofibrillary tangles. Our finding that PHF-like structur es assemble from a MAP-2 fragment raises new questions about MAP-2's r ole in the etiology of Alzheimer's Disease. (C) 1996 Academic Press, I nc.